Artificial, Parallel, Left-Handed DNA Helices

This communication reports an engineered DNA architecture. It contains multiple domains of half-turn-long, standard B-DNA duplexes. While each helical domain is right-handed and its two component strands are antiparallel, the global architecture is left-handed and the two component DNA strands are oriented parallel to each other

Retrosynthetic Analysis-Guided Breaking Tile Symmetry for the Assembly of Complex DNA Nanostructures

Current tile-based DNA self-assembly produces simple repetitive or highly symmetric structures. In the case of 2D lattices, the unit cell often contains only one basic tile because the tiles often are symmetric (in terms of either the backbone or the sequence). In this work, we have applied retrosynthetic analysis to determine the minimal asymmetric units for complex DNA nanostructures. Such analysis guides us to break the intrinsic structural symmetries of the tiles to achieve high structural complexities. This strategy has led to the construction of several DNA nanostructures that are not accessible from conventional symmetric tile designs. Along with previous studies, herein we have established a set of four fundamental rules regarding tile-based assembly. Such rules could serve as guidelines for the design of DNA nanostructures

Isothermal Self-Assembly of Spermidine–DNA Nanostructure Complex as a Functional Platform for Cancer Therapy

Programmable DNA nanostructure self-assembly offers great potentials in nanomedicine, drug delivery, biosensing, and bioimaging. However, due to the intrinsically negatively charged DNA backbones, the instability of DNA nanostructures in physiological settings poses serious challenges to their practical applications. To overcome this challenge, a strategy that combines the magnesium-free DNA self-assembly and functionalization is proposed in this study. We hypothesize that naturally abundant spermidine may not only mediate the self-assembly of DNA nanostructures, but also shield them from harsh physiological environments. As a proof of concept, a DNA nanoprism is designed and synthesized successfully through spermidine. It is found that spermidine can mediate the isothermal self-assembly of DNA nanoprisms. Compared to conventional Mg²⁺-assembled DNA nanostructures, the spermidine–DNA nanoprism complex shows higher thermal stability and better enzymatic resistance than Mg²⁺-assembled DNA nanoprisms, and more importantly, it has a much higher cellular uptake efficacy in multiple cancerous cell lines. The internalization mechanism is identified as clathrin-mediated endocytosis. To demonstrate the suitability of this new nanomaterial for biomedical applications, an mTOR siRNA, after being conjugated into the complex, is efficiently delivered into cancer cells and shows excellent gene knockdown efficacy and anticancer capability. These findings indicate that the spermidine–DNA complex nanomaterials might be a promising platform for biomedical applications in the future

Whole blood test results of subjects after returning to Chongqing.

<p>Data are given as the mean ± SD. RBC  =  red blood cell, Hb  =  hemoglobin, Hct  =  hematocrit, MCV  =  mean corpuscular volume, MCH  =  mean corpuscular hemoglobin, MCHC  =  mean corpuscular hemoglobin concentration, RDW  =  red blood cell volume distribution width, WBC  =  white blood cell, Neu  =  neutrophil. ^*<i>P</i><0.05, relative to baseline, ^&<i>P</i><0.05, relative to high altitude values, ^#<i>P</i><0.05, relative to 3^rd day values, ̂<i>P</i><0.05, relative to 50^th day values, ^△<i>P</i><0.05, relative to the control group.</p

pH, PaO2, PaCO2, and SaO2 of subjects after returning to Chongqing.

<p>Data are given as the mean ± SD. ^*<i>P</i><0.05, relative to baseline, ^&<i>P</i><0.05, relative to high altitude values recorded at 6 months, ^△<i>P</i><0.05, relative to the control group</p

Symptom scores.

<p>Data are presented as mean ± SD. *<i>P</i><0.05, relative to the Chongqing group. ̂<i>P</i><0.05, relative to the 3^rd day, ^#<i>P</i><0.05, relative to the 50^th day.</p

Serum CK, CK-MB, and LDH of subjects after returning to Chongqing.

<p>Data are given as the mean ± SD. CK  =  creatine kinase, CK-MB  =  creatine kinase–MB, LDH  =  lactate dehydrogenase. ^*<i>P</i><0.05, relative to baseline, ^&<i>P</i><0.05, relative to high altitude values, ^#<i>P</i><0.05, relative to 3^rd day values, ̂<i>P</i><0.05, relative to 50^th day values, ^△<i>P</i><0.05, relative to the control group.</p

Rates of change in symptom scores.

<p>Data are presented as mean ± SD. Symptom scores recorded on the 3^rd day after return to low-altitude areas served as baseline values. Rate of change 1 = (score on 50^th day-score on 3^rd day)/score on 3^rd day×100%; rate of change 2 = (score on 100^th day-score on 3^rd day)/score on 3^rd day×100%. Rates of change 1 and 2 showed no significant difference between the Chongqing and Kunming groups (<i>P</i>>0.05).</p

Classification and scoring criteria of the symptoms of high-altitude de-acclimatization syndrome.

<p>Classification and scoring criteria of the symptoms of high-altitude de-acclimatization syndrome.</p

Grading of high-altitude altitude de-acclimatization syndrome.

<p>Grading of high-altitude altitude de-acclimatization syndrome.</p